The present proposal is a supplement to the recently funded NeuroHIV Magnetic Resonance Spectroscopy Consortium grant (PI: Navia R01NS036524-05). The parent grant is a longitudinal study of brain metabolite changes and cognitive impairment associated with advancing HIV disease in the era of anti-retroviral therapy (ART). This supplement aims to support state-of-the-art longitudinal analyses of the structural MRI data that is automatically collected as part of the parent consortium grant. The present study will allow us to identify multiple MRI signatures of brain dysfunction associated with HIV, and in turn define the evolutionary stages of brain involvement in HIV. ART has dramatically improved survival rates among HIV patients, though the extent to which these agents provide lasting benefits to the brain remains unresolved. There is accumulating evidence that despite good peripheral viral suppression, a significant amount of HIV-associated brain injury continues to occur. In vivo volumetric magnetic resonance imaging (MRI) provides a sensitive measure of regional and specific HIV- associated brain abnormalities. The MRS Consortium is collecting neuroimaging, immunological/virological and cognitive data from 310 HIV subjects with a history of advanced HIV disease on stable ART and at different stages of immunological and neurocognitive compromise. Follow-up assessments occur every 26-32 weeks (including MRI). The T1 and dual echo (proton density/T2) sequences from each time point will be analyzed using semi-automated methods including segmentation, voxel based morphometry and automatic anatomical labeling in order to ascertain the extent and severity morphometric change in treated HIV patients. The primary aims include: 1) To examine the evolution/progression of brain parenchymal fraction (BPF), frontal lobe, basal ganglia, hippocampal, and corpus callosum atrophy associated with HIV infection relative to MRS markers of inflammation (Ml/Cr, and Cho/Cr) and neuronal health (NAA/Cr); 2) To assess the temporal relationships between change in MRS measures, volumetric loss, and progression of cognitive impairment; and 3) To identify host and viral factors (e.g., age, CD4 count, chemokines, and HIV RNA) that may predict risk for structural brain atrophy. We propose to derive multivariate longitudinal models and examine the CMS effects of HIV as a dynamic system of interrelated factors. The establishment of neuroanatomical sequelae among HIV subjects on ART will have critical ramifications for cognitive outcome as well as provide additional targets for therapeutic outcome. [unreadable] [unreadable] [unreadable]